儿童哮喘中LCK通过促进AP-1/ETS1协同转录调控CD28表达影响Th1/Th2细胞平衡的机制研究

儿童哮喘（childhood asthma，CA）严重影响儿童的身心健康，逐渐成为亟待解决的社会热点问题。文献报道Th1/Th2细胞失衡是导致CA的重要机制之一，因此深入探究Th1/Th2失衡的分子机制对于CA的防治具有重要意义。本项目前期研究结果表明，ETS1在哮喘儿童分离的外周血淋巴细胞中高表达且ETS1过表达促进儿童CD4+ T细胞向Th2细胞分化，但具体机制不明。结合文献调研及前期研究结果，我们推测LCK通过促进AP-1/ETS1协同转录来调控CD28表达，从而影响Th1/Th2细胞平衡，进而参与CA的发病进程。本研究拟从临床、细胞和动物三个层次探讨LCK/AP-1/ETS1/CD28影响Th1/Th2平衡参与CA的分子机制，以期为CA有效防治策略的提出和新靶点药物的研发提供重要依据。

Childhood asthma (CA) seriously affects the physical and mental health of children, and gradually becomes a hot social issue that needs to be solved. It has been reported that Th1/Th2 imbalance is one of the important mechanisms leading to CA. Therefore, it is of great significance to study the molecular mechanism of Th1/Th2 imbalance for the prevention and treatment of CA. Our previous study indicates that ETS1 is highly expressed in peripheral blood lymphocytes isolated from asthmatic children, and ETS1 overexpression promotes CD4+ T cells to differentiate into Th2, but the specific mechanism is not yet known. Based on the literature survey and previous work, we speculate that LCK may regulate the expression of CD28 by promoting AP-1/ETS1 cooperative transcription to affect Th1/Th2 balance and then participate in the pathogenesis of CA. This study intends to explore the molecular mechanism of LCK/AP-1/ETS1/CD28 affecting Th1/Th2 balance and participating in CA from clinical, cellular and animal levels, providing an important basis for the proposal of effective prevention and treatment strategies and the development of new target drugs for CA.